Investigations On the Fish Acute Toxicity of Fragrance Ingredients Involving Chinese Fish Species and Zebrafish Embryos

Abstract

While zebrafish (Danio rerio) have been accepted worldwide for evaluating chemical hazards to aquatic vertebrates, and in some countries it is mandated to generate fish toxicity data using native species, such as Chinese rare minnow (Gobiocypris rarus) in China. This represents an additional regulatory constraint that may cause redundant tests, additional animal uses, and higher costs. Previous studies showed that juvenile G. rarus was more sensitive than zebrafish juveniles and embryos to metals. To better understand the sensitivity of G. rarus to organic chemicals, we selected 29 fragrance ingredients belonging to various chemical classes and with differing physicochemical properties, for which good quality zebrafish acute toxicity data were available and tested them with juvenile G. rarus and embryo D. rerio using the Organisation of Economic Co-operation and Development test guidelines. Chemical toxicity distribution (CTD) and chemical ratio distribution (CRD) models were established to systematically compare the sensitivity between juveniles of G. rarus and D. rerio, as well as between D. rerio embryos and juveniles. The results of the CTD models showed that for tested chemicals, the sensitivity of juvenile G. rarus was similar to that of D. rerio juveniles and embryos. The CRD comparisons revealed that juvenile G. rarus was slightly less sensitive by a factor of ~2 than juvenile D. rerio to ingredients belonging to Verhaar class 3 and Ecological Structure Activity Relationship ester class, while comparable to other chemicals. These comparative experiments demonstrated that fish toxicity data with G. rarus can be submitted for use in chemical registrations outside China, which would avoid repeating animal tests using D. rerio. Meanwhile, the similar sensitivity of zebrafish juveniles and embryos to fragrance ingredients confirmed the suitability of replacing juveniles by zebrafish embryos.

Human Apparent Volume of Distribution Predicts Bioaccumulation of Ionizable Organic Chemicals in Zebrafish Embryos

“…With the restriction of using vertebrates in toxicity tests, zebrafish embryos have become a promising alternative for fish bioaccumulation and toxicity tests because many studies found similar sensitivity to diverse chemicals across embryo and later fish life stages, 69 though age specific exceptions have also been reported. 49 Herein, we systematically examined the toxicokinetic processes of eight pharmaceuticals with diverse physicochemical properties and pharmacokinetic attributes using zebrafish embryos as a model aquatic species, and then applied the human pharmacokinetic parameter V D to develop predictive fish bioconcentration models.…”